CLINICAL CORE: ABSTRACT The Pacific Northwest Udall Center (PANUC) Clinical Resource Core has recruited and characterized a cohort of more than 600 individuals with PD during the initial funding period. Data from the PANUC Clinical Resource Core, in collaboration with other Udall Centers and other academic medical centers, have helped confirm Apolipoprotein E (APOE) and glucocerebrosidase (GBA) as genes which are relevant to the pathogenesis of cognitive decline in Parkinson's Disease (PD). Understanding the mechanisms underlying these gene effects is the focus of this renewal application, utilizing both model systems (Projects 1 and 2) and human subjects (Projects 3 and 4). The Clinical Resource Core will provide well-characterized PD and control subjects of appropriate genotypes for Projects 3 and 4. In addition, select members of the existing cohort will be retained for additional longitudinal clinical and neuropsychological testing follow-up to support ongoing genetic and biomarker studies, with a refined battery of tests and a reduced frequency of visits designed to maximize efficiency. Gait and balance testing will be added to the test battery as an innovation that is thought to reflect higher order CNS function closely related to cognition. This innovation leverages the expertise of Dr. Horak, an investigator introduced to the PANUC by way of PANUC pilot award funding during the last funding period. As in the first cycle, Clinical Resource Core subjects will be followed at two sites: one at UW directed by Dr. Hu, and the other at OHSU directed by Dr. Quinn. Dr. Horak will oversee gait and balance testing at both sites.